Bone Morphogenetic Protein 1  (骨形态发生蛋白 1)

骨形态发生蛋白 1 (BMP-1) 又称金属蛋白酶，属于 BMP-1/tolloidlike 蛋白酶 (BTP)^[1][2]。已知 BTPs 参与肌肉生长和体内平衡的控制，以及伤口愈合和组织修复。BMP-1 是一种标志性的细胞外基质 (ECM) 蛋白，与乳腺肿瘤的高转移潜力相关^[3]。BMP-1 能够加工成熟功能细胞外基质 (ECM) 蛋白的前体和一些生长因子，包括 TGFβ、BMP2、BMP4 和 GFD8，调节形态发生^[4]。BMP-1 是出生后肺成纤维细胞中占主导地位的 C 蛋白酶，介导 I 型前胶原 COOH 羧基末端前肽 (CICP) 的裂解，主要作用位点为细胞外间隙^[1]。BMP-1 能够维持适当水平的 I 型前胶原及其活化产物，是维持牙周内稳态和正常牙骨质形成的重要组成部分。血栓反应蛋白-1 (TSP-1) 是一种 ECM 蛋白，因其调节细胞-基质相互作用的能力而被分类为“基质细胞”，TSP-1 的切割将导致 BMP-1 过表达。然而，BMP-1 在富含 TSP-1 的微环境中既能触发细胞黏附的破坏，又能刺激 TGF-β 信号通路，促进原代人角质细胞向肌成纤维细胞分化。因此，BMP-1 参与一些发育和生理过程，如软骨和骨形成，肌肉生长和体内平衡^[2][3]。BMP-1 基因突变导致人类成骨不全，即骨骼紊乱，其特征是易骨折、骨脆，或导致小鼠的牙周病和皮肤脆弱表型^[3]。BMP-1-3 是一种新型的全身骨修复调节因子，是 BMP-1 基因的亚型，在人体血浆中循环，促进骨愈合。体外 BMP-1-3 增加了 MC3T3-E(1) 成骨细胞样细胞中 I 型胶原蛋白和骨钙素的表达，并增强了骨髓间充质干细胞的矿化骨结节的形成^[4]。

Bone morphogenetic protein 1 (BMP-1) also known as metalloprotease, belonging to the BMP-1/tolloidlike proteinases (BTP) family^[1][2]. BTPs are known to be involved in the control of muscle growth and homeostasis and in wound healing and tissue repair, and BMP-1 is a signature extracellular matrix (ECM) proteins associated with the high metastatic potential of breast tumors^[3]. BMP-1 regulates morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8^[4]. BMP-1 is the dominant C-proteinase in postnatal lung fibroblasts and mediates cleavage of COOH-terminal propeptide of type I procollagen (CICP) with the main action site of extracellular space^[1]. BMP-1 maintains appropriate levels of procollagen I and its activated products, acts as an essential part for maintaining periodontal homeostasis and normal cementum formation^[2]. The cleavage of thrombospondin-1 (TSP-1), an ECM protein classified as “matricellular” for its ability to regulate cell-matrix interactions, results BMP-1 overexpression. However BMP-1 can both trigger the disruption of cell adhesion and stimulate TGF-β signaling in TSP-1-rich microenvironments, which promote the differentiation of primary human keratocytes into myofibroblasts^[3]. Thereby, BMP-1 participates in several developmental and physiological processes such as cartilage and bone formation, muscle growth and homeostasis^[2][3]. Mutations of BMP-1 gene cause osteogenesis imperfecta in human, a bone disorder characterized by brittle bones that are prone to fracture, or phenotypes of periodontal disease and skin fragility in mice^[3]. BMP-1-3 is a novel systemic regulator of bone repair. BMP-1-3 isoform of the BMP-1 gene circulates in the human plasma and enhances bone healing. In vitro BMP-1-3 increases the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhances the formation of mineralized bone nodules from bone marrow mesenchymal stem cells^[4].

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